Sandhoff’s disease is a rare inherited genetic disorder characterized by degeneration of the central nervous system. It usually appears before the age of 6 months. Its management currently consists of treating the associated symptoms.

Definition of Sandhoff’s disease

Sandhoff’s disease is a rare genetic disease known as lysosomal. This means that it induces a malfunction of the lysosome, a vesicle present in the cells of the organism and necessary for the “recycling” of intracellular waste. Some of them can thus accumulate within cells and have serious consequences on the functioning of the organism.

In Sandhoff’s disease, there is central nervous system damage caused by an accumulation of GM2-type gangliosides in neurons and peripheral tissues. As such, Sandhoff’s disease is said to be GM2 gangliosidosis.

Cause of Sandhoff’s maladie

Sandhoff’s disease is caused by genetic mutation on chromosome 5 (5q13). This leads to a defect in the production of lysosomal enzymes, that is to say of proteins involved in the recycling and elimination of cellular waste.

This production defect relates more specifically to one of the two subunits of the hexosaminidase A and B enzymes involved in the degradation of gangliosides of the GM2 type. These compounds accumulate in neurons and peripheral tissues, affecting the functioning of the central nervous system.

People affected by Sandhoff’s disease

Sandhoff’s disease is an inherited autosomal recessive disease. This means that it can affect both the female sex and the male sex. For the disease to develop, the mutation must affect both copies of the gene. Each is inherited from one of the parents. In other words, each parent is himself the carrier of a genetic anomaly in one of his copies of the gene, without being sick himself.

Sandhoff’s disease mainly occurs in infants, although there are rare cases where it occurs in older children and adults. There are also three forms depending on the age of onset of the disease:

• type 1 or early infantile form, which is the most common form starting between 3 and 6 months;
• type 2 or juvenile form, which is a rare form occurring between 2 and 6 years of age;
• type 3 or adult form, when Sandhoff’s disease appears after the age of 10 years.

In Europe, the prevalence of Sandhoff’s disease is estimated at one case per 130 births.

Diagnostic of Sandhoff’s maladie

A clinical examination can see the frequent symptoms of Sandhoff’s disease and guide the diagnosis.

An enzymatic assay is then necessary to distinguish Sandhoff’s disease from a disease with similar characteristics: Tay-Sachs disease. If these two diseases are lysosomal diseases and GM2 gangliosidoses, they differ in the presence of certain lysosomal enzymes (proteins involved in the recycling and elimination of cellular waste). Only the production of hexosaminidase A is affected in Tay-Sachs disease while the production of hexosaminidases A and B is impaired in Sandhoff’s disease.

The most frequently observed symptoms are:

• the inexhaustible bursts of noise;
• early blindness;
• progressive motor deterioration;
• progressive mental deterioration;
• macrocephaly (excessive development of the skull);
• a cherry red spot on the macula (specific area of ​​the retina).

Other symptoms can also manifest themselves as:

• a chubby face;
• hepatosplenomegaly (enlargement of the liver and spleen).

Symptomatic treatments

There is currently no specific treatment for Sandhoff’s disease. Symptomatic treatments are offered to combat the symptoms of the disease. Antiepileptics can, for example, be prescribed. Motor and respiratory physiotherapy can also be implemented.

Treatments in research phase

A lot of research is being done to provide an effective treatment for Sandhoff’s disease. Gene therapy is a promising treatment for genetic diseases. It involves introducing genetic material into affected cells or tissues to treat a disease. Enzyme therapy is another avenue under study for the treatment of Sandhoff’s disease. It could make it possible to inhibit the production of glycosphingolipids responsible for neurological damage.

To date, there are no preventive measures for Sandhoff’s disease. Prevention consists above all in early detection of the disease.